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Curr Opin Otolaryngol Head Neck Surg. Author manuscript; available in PMC 2012 October 01.
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Published in final edited form as:
Curr Opin Otolaryngol Head Neck Surg. 2011 October ; 19(5): 376–381. doi:10.1097/MOO.
0b013e32834a5be1.
EFFERENT MODULATION OF HAIR CELL FUNCTION
RICHARD D. RABBITT1,2 and WILLIAM E. BROWNELL3
1Department of Bioengineering, University of Utah, Salt Lake City, UT, USA
2Marine
Biological Laboratory, Woods Hole, MA, USA
3Department
of Otolaryngology, Head and Neck Surgery, Baylor College of Medicine, Houston,
TX, USA
Abstract
Purpose of review—This review covers papers published between 2010 and early 2011 that
presented new findings on inner ear-efferents and their ability to modulate hair cell function.
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Recent findings—Studies published within the review period have increased our understanding
of efferent mechanisms on hair cells in the cochlear and vestibular sensory epithelium and provide
insights on efferent contributions to the plasticity of bilateral auditory processing. The central
nervous system controls the sensitivity of hair cells to physiological stimuli by regulating the gain
of hair cell electromechanical amplification and modulating the efficiency of hair cell-8th nerve
transmission. A notable advance in the past year has been animal and human studies that have
examined the contribution of the olivocochlear efferents to sound localization particularly in a
noisy environment.
Summary—Acoustic activation of olivocochlear fibers provides a clinical test for the integrity of
the peripheral auditory system and has provided new understanding about the function and
limitations of the cochlear amplifier. While similar tests may be possible in the efferent vestibular
system they have not yet been developed. The structural and functional similarities of the sensory
epithelia in the inner ear offer hope that testing procedures may be developed that will allow
reliable testing of the vestibular hair cell function.
Keywords
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olivocochlear; hearing; efferent vestibular system; balance; descending control; bilateral
integration
INNER EAR EFFERENTS
INTRODUCTION
This review covers papers that enhance our understanding of how the brain modulates inner
ear mechanoreception. Hair cell activity can be modulated by altering the magnitude of the
mechanical stimulus that reaches the inner ear either by activation of middle ear muscles to
attenuate sound or by changing the position or angular acceleration of the head with skeletal
muscles. Inner ear hair cells differ from most sensory cells in receiving efferent innervation
Correspondence to William E. Brownell, Oto-HNS, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.
[email protected]; tel: 713-798-8540; fax: 713-798-8553..
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from neurons located in the brain. There are two innervation patterns, one is directly onto
the hair cell body and the other is onto eighth nerve dendrites. The former has been called
presynaptic and the latter postsynaptic in relation to their presumed impact on the
neurotransmission at the hair cell-eighth nerve synapse. Presynaptic efferent activity can
affect neurotransmitter release but it can also modulate the gain of mechanical force
generation by the hair cell. Two types of hair cell electromechanical force generation have
been identified; one is somatic outer hair cell (OHC) electromotility [1, 2] and the other is a
stereocilia bundle motor [3, 4].
Medial olivocochlear OC (MOC) efferents are myelinated fibers that innervate OHCs in
mature animals. They modulate cochlear mechanics and otoacoustic emissions (OAE, which
include: distortion product, DPOAE; spontaneous, SOAE; click evoked, COAE; etc).
Lateral OC (LOC) efferents innervate auditory-nerve fibers under inner hair cells (IHCs)
and directly modulate the firing of the auditory eighth nerve fibers. There is a direct efferent
innervation onto Type II hair cells in the vestibular sensory epithelia. Calyceal afferent
endings interfere with a somatic contact onto Type I hair cells but a single efferent can
innervate both the Type II cell body presynaptically and a calyceal terminal
postsynaptically. The MOC and LOC cell bodies of origin and the anatomical trajectory of
their axons to the inner ear have been established, but efferent vestibular system (EVS)
neurons are scattered in clusters that do not divide cleanly into two systems.
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This review builds on an excellent review of auditory olivocochlear efferents that appeared
last year in this journal [5]. We identify new findings and encourage the reader to look to
last year's review for background. The past year has seen a new review of the EVS [6] that
provides a context for several new fundamental findings including the first observation of
efferent modulation of hair cell force production in the semicircular canals [4]. Another
excellent review of physiological principles underlying efferent inhibition in both vestibular
and auditory hair cells appeared this year [7]*. Additional background information may also
be found in a new book entitled “Auditory and Vestibular Efferents” that has just been
published [8].
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MOC activation alters outer hair cell electromotility—We have previously shown
how current shunting caused by MOC efferent activity in a piezoelectric model of the OHC
can result in reduced electromotility and thereby alter cochlear amplification [9]. The model
results were consistent with and improved on earlier models that offered an explanation for
the suppression of cochlear amplification observed in physiological, behavioral and human
experiments [5]. The past year has seen a number of experimental studies that confirm and
extend the fundamental finding that MOC activity alters cochlear amplification by acting on
OHC electromotility.
Behavioral studies with chinchillas demonstrated a reduction of cochlear sensitivity during
selective attention to visual stimuli [10]. The investigators found a decrease of cochlear
sensitivity during the period of attention to visual stimuli but not when attending to an
auditory task, demonstrating that the decrease is related to selective attention to visual
stimuli rather than to arousal level. Since the effect is present early in sensory transduction
the authors suggested it was mediated by activation of olivocochlear efferent fibers. The
authors have tested this hypothesis by stimulating MOC efferent axons in chinchillas with
sectioned middle-ear muscles, while recording cochlear potentials [11]. MOC stimulation
produced CAP amplitude suppression of and CM amplitude increments similar (but
somewhat smaller) than those found in studies on other animals, supporting their suggestion
that the visual attention effects could have been mediated by olivocochlear activation. This
finding is consistent with the broader hypothesis that efferent innervation of the inner ear
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plays an important role in sensory integration and modulation inner ear afferent inputs to
meet the behavioral needs of the organism.
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Fast and slow olivocochlear effects in humans—Physiological studies have shown
that the MOC system modulates basilar membrane and auditory nerve activity on both a fast
(10–100 ms) and slow (10–100 s) time scale. The fast effect is thought to result from current
shunting while the slow effect may result from a G-protein mediated change in OHC lateral
wall mechanics. The slow effect has been postulated to aide in protection against acoustic
trauma. A recent study explored the slow effect in humans by looking at the effect of
contralateral acoustic stimulation on spontaneous otoacoustic emissions [12, 13]. Fast and
slow effects were observed but with a high threshold and small effect magnitude for the
slow effect.
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Olivocochlear effects in the processing of auditory localization cues—There is
a rich history of experimental and model data supporting a contribution of the MOC system
in detecting relevant signals in a noisy background [5]. A systematic study of the response
of cat single auditory nerve fibers suggests that the MOC system has a greater effect on low
spontaneous rate fibers than on high spontaneous rate fibers [14]. Broad band noise that was
shaped by one of ten head related transfer functions (HRTF) was presented to the ear in the
presence and absence of noise. HRTF capture the effect of the cat's head shape on the sound
arriving at the tympanic membrane and contains cues that are relevant for sound
localization. There were population differences between fibers having a spontaneous firing
rate of ≤ 1 spike/sec and those ≥ 18 spikes/sec. A reasonable interpretation of the differences
was that activation of the MOC system expanded the intensity range over which the low
spontaneous range fibers encode the HRTF information. Low and high spontaneous fibers
arise from inner hair cells and why activation of the outer hair cell by the MOC results in
different coding behavior at synapses on the same cell remains a mystery. This might reflect
an MOC dependent nonlinearity, or it is also possible that LOC activation might combine
systematically with MOC to shape the afferent discharge.
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The membrane properties and synaptic responses of neurons in the mouse lateral superior
olivary nucleus (LSO) were measured in a brain slice preparation [15]. The neurons could be
divided into two populations based on their response latencies, ion channels and
pharmacology. The authors concluded the short response latency neurons were the principal
cells of the LSO involved in processing interaural intensity differences and projecting to the
inferior colliculus. They postulated the slower population consisted of the cell bodies of
origin for the LOC neurons that project to the afferent fibers in the IHCs in the ipsilateral
cochlea. If the identity of the slower population is unequivocally identified their
observations could be useful in modeling the effect of LOC activity on hearing.
Olivocochlear effects on sound localization—Two notable auditory localization
studies were published during the past year that examined OC effects on sound localization,
one in ferrets [16]* and the other in humans [17]**. An earlier animal study [18] examined
the effect of OC lesions on the ability of cats to localize a sound source in the presence of
noise. Bilateral OC lesions were made at locations that should cut most of the crossed and
uncrossed MOC efferent fibers. Performance in noise was worse immediately after the
lesions and all three lesioned animals showed some compensation with one returning to prelesion values after 6 sessions. The study was consistent with earlier studies on the MOC
mediated improvement in detection of a signal in a noisy background but the improvement
provoked questions as to the basis of the neural plasticity that allowed for compensation.
A behavioral study [16] looked at the effect of lesions on the ability of ferrets to compensate
for the introduction of an earplug in a sound localization task. The animals received a
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parasaggital lesion of the OC either at the midline or to one side of the midline. Histological
examination of the cochlea confirmed that LOC innervation was greatly diminished and the
MOC partially spared in the ear on the same side as the lateral lesion (OC innervation in the
contralateral ear appeared normal). The midline lesions were assumed to remove MOC input
in both ears while preserving LOC input. All the lesioned animals learned to localize a one
second sound (without noise) and localization was compromised following the introduction
of an earplug. The control and the lateral lesion groups showed a modest improvement in
their ability to localize over a 10 day plug period and both returned to preplug performance
when the plug was removed. The lateral lesion group showed a similar loss of localization
on plugging but did not compensate and they also returned to normal performance when the
plug was removed. The results indicate that intact MOC innervation is required for the
relearning of sound localization cues when input from one ear is compromised and that a
single ear, with intact efferent innervations, is sufficient for rebalancing the processing of
the binaural cues involved in localization.
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Subjects in the human study identified which of 8 speakers emitted a short, band-pass burst
embedded in a longer noise stimulus that was played on all eight speakers. Signal to noise
ratio and the location of the sound were randomly varied. Sound localization results were
compared with a variety of OAE measures including the magnitude of the OC-reflex. The
ability to localize in noise as well as in the magnitude of the OC-reflex suppression were
highly variable as has been previously reported. However, the magnitude of each measure
covaried, with individuals having the greatest OC-reflex suppression tending to perform best
in detecting the speaker in a noisy environment. This is the first study to demonstrate a
relation between OC-activity and sound localization in humans and lends further support to
the view that the OC-reflex facilitates sound-localization in the presence of background
noise particularly at low signal to noise ratios.
A study in women [19] identified one of the factors that may contribute to OC-reflex
variability. The investigators looked at the time the test was performed during the ovarian
cycle (as defined by oestradiol and progesterone serum levels and menstrual cycle dating).
OAEs including SOAEs and TEOAEs, ABRs and MOC suppression of TEOAEs were
measured. There were correlations with the cycle including a significant negative correlation
of MOC suppression with oestradiol levels in the follicular phase. The results of the study
show small changes in auditory function during the ovarian cycle but they are suggestive of
an increased hearing sensitivity including MOC suppression around the time of ovulation.
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Olivocochlear effects in overshoot—Overshoot is a psychophysical effect where a
brief sound has a lower threshold when presented 100 ms or more after the start of a noise
burst compared to its threshold near the start of the noise burst. Last year's review [5]
described a study in which a behavioral measure of overshoot and an OAE-based measure
that resembled overshoot in all but one of the same subject population [20]. Another study
[21] by the same investigators provided further support for the role of the MOC system in
overshoot. Very short (10 ms) tones were masked by a 400 ms noise burst. Detection
improvement reached a temporary plateau between 10–30 ms, after which a steady
improvement with time occurred. Similar plateaus have been reported in physiological
studies of MOC effects.
A computational model was used to evaluate two possible mechanisms for psychophysical
overshoot, adaptation and MOC efferent feedback [22]. The influence of model variables for
the detection of a tone-pip in a broadband noise revealed the MOC feedback was essential to
produce overshoot. The analysis supports the hypothesis that the noise burst elicits MOC
activity leading to a decrease in cochlear-amplifier gain that reduces the response to the lowlevel noise more than it reduces the response to the brief, high-level tone.
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Olivocochlear effects on auditory system development in a noisy environment
—The possible involvement of the MOC system in auditory system development was
discussed in last year's review [5]. A recent study examined its involvement in mediating the
deleterious effects of noise on cochlear development [23]. A population of knock-out mice
with a homozygous null mutation of the α9 nicotinic acetylcholine receptor subunit (α9KO)
were raised in a noisy environment and their ability to process auditory stimuli was assessed
behaviorally (startle response) and physiologically (ABR). Their results were compared with
another population of the knock-out mice raised in a normal acoustic environment as well as
a population of control mice raised in both the noisy and quite environments. The α9
nicotinic acetylcholine receptor subunit is found on OHCs postsynaptic to the MOC
terminals and hair cells that do not have it are unable to respond to MOC activation. The
knock-out mice raised in the presence of noise were less able to process rapid temporal
information and showed elevated ABR thresholds in the middle frequencies. DPOAE
generation was not affected but a change in wave 2 of the ABR was noted suggesting a
modification of synaptic activation in the cochlear nucleus. The results suggest that the
MOC system is required for the development of normal connections in the CNS in an
abnormal noisy environment.
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Efferent Vestibular System (EVS)—Anatomical evidence of the extensive efferent
innervation of the inner ear began to appear in the early 20th century [24–26]. Phylogenetic
observations highlight the ancient origin of efferent of neural pathways and draws attention
to the fundamental importance of efferent action in both auditory and vestibular sensation
[27–29]. Mechanisms of efferent action in the more primitive vestibular organs therefore are
likely to have relevance to efferent action in the cochlea. The anatomy and physiology of the
efferent vestibular system are reviewed this year in extensive articles by Holt et al. [6] and
Wersinger & Fuchs [7].
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Historical evidence in-vivo suggests that a primary function of the EVS is to tune vestibular
sensation to the interest and needs of the organism, for example by decreasing the sensitivity
during large self-generated movements [30, 31], and adjusting the background discharge
characteristics of afferents [6]. The decrease in sensitivity appears to have principal origins
in efferent inhibition of hair cell electrical responses through inhibitory post-synaptic
potentials [3], opening of basolateral ion channels [6], and a concomitant decrease in hair
cell receptor potential modulation [3, 32]. Although EVS effects on vestibular signal
encoding are profound in situ, and have been observed in some species in vivo, the same
level of EVS control has not been demonstrated in primates [33]. It is not yet known if there
are fundamental interspecies differences in EVS action, or if experimental conditions such
as the level of attention or relevance of the stimulus to the needs of the animal might be at
play. There remains a paucity of single unit recordings from efferent vestibular neurons and
a lack of information regarding specific sensory stimuli or states of attention that evoke
changes in EVS activity. Clearly electrical activation of the brainstem efferent vestibular
nucleus has substantial effects on vestibular sensation and neural coding, but when and how
the system is activated under normal physiological conditions remains speculative.
Sensitivity modulation prior to self-induced movements has been shown, but very little is
known about dynamic responses of efferent vestibular neurons to traditional vestibular
movement stimuli, let alone responses driven by multisensory integration, bi-lateral
balancing, or dynamic optimization of signal to noise analogous to that achieved in the
mammalian cochlea.
The primary mechanisms of EVS activation alter the electrical excitability of hair cells and
afferent neurons, acting primarily through nicotinic cholinergic receptors (nAChRs),
secondarily through muscarinic receptors (mAChRs) [6, 34, 35], and several apparently less
understood transmitters and receptors [6]. EVS activation also decreases semicircular canal
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hair bundle motion in response to low strength mechanical stimuli [4], but this mechanical
effect is quite small relative to the electrical effects. Nevertheless, the observation of EVS
inhibition of active hair bundle movements in a teleost vestibular organ suggests that neural
control of hair cell mechanical amplification predates the appearance of outer hair cells in
the mammalian cochlea. Efferent control of bundle-based amplification in non-mammalian
hearing organs might be a general principle, such as control of short hair cell bundle-based
amplification in the avian auditory papilla. The biophysics underlying efferent control of
hair bundle mechanical amplification is not entirely clear [3], but has been speculated to be
controlled by somatic electrical shunting [36]. Both electrical and mechanical actions of
efferent innervation in the vestibular system may have particular relevance to efferent action
in the low-frequency apical region of the mammalian cochlea.
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Kinetics of efferent action on hair cells—Inner ear hair cell organs transduce signals
with frequencies ranging from zero (gravity) to nearly 100kHz in some mammals. The
kinetics of efferent action on hair cells follows a wide range of time courses, presumably
reflecting needs of the animal and specializations of specific hair cell sensory organs [3, 32,
37]. Recent evidence suggests timing differences might partially involve the spatial
distribution of channels/receptors and intracellular organelles that alter reaction-diffusion
kinetics and temporal properties of intracellular calcium signaling [7]*. Pulsed infrared laser
stimuli has been shown to evoke transient mitochondrial calcium currents [38], thus
modulating synaptic transmission from vestibular hair cells with a delay of ~7ms [39]. This
form of stimulation might prove useful to investigate temporal responses of hair cells to
optically controlled calcium transients.
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Efferent involvement in tuning bilateral sensory integration—Both the auditory
and vestibular systems integrate bilateral information at brainstem nuclei. Both systems are
characterized by the convergence of topographically organized input onto topographically
organized neurons (similar frequency inputs from both ears to the superior olivary nuclei
and input from mirror end organs to the vestibular nuclei). The conduction time for the
information to arrive at the midline nuclei must be regulated within close tolerances [40] and
a peripheral insult would be expected to alter timing. The total conduction time includes the
time for action potentials to traverse the conduction pathways as well as for dendritic
integration and synaptic delays. Axonal conduction velocity is determined by fiber diameter
and involves axonal-glial signaling to adjust the internodal length between nodes of Ranvier
and the thickness of the myelin sheath [40, 41]. Both sensory modalities have sufficient
plasticity to compensate for either temporary or permanent insult to the inner ear.
Compensation for damage to the end organ is most likely an extreme example of a normal
tuning of the conduction time that must occur to optimize bilateral sensory integration. The
efferent innervation to the periphery originates from neurons located in and around the very
nuclei that process bilateral information so they are ideally poised to monitor the timing and
activate the requisite feedback mechanisms.
The OC and EVS efferent systems release acetylcholine and the comparison with motor
systems has often been made. Efferents to the lateral line organs fire with motor neuron
activation of the muscles involved in swimming [42] and our middle ear muscles are
activated by speech. Other agents are also released at efferent terminals that could be part of
second messenger signaling either for activating maturation or maintaining system
tolerances. Inner ear efferent activation may be associated with motor activity such as
bruxism and myoclonic jerks for which there is no known function. Bruxism generates loud
bone conducted sounds that would essentially activate both ears simultaneously. Myoclonic
jerks will activate the vestibular epithelia. Speculatively, the midline auditory and vestibular
nuclei could assess whether the conduction time is appropriate. If not, the efferent fibers
would signal the afferent fibers to adjust conduction velocity appropriately.
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CONCLUSION
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Research on the effects of efferent activity on hair cells has provided insight on the function
and feedback control of inner ear mechanoreceptor sensory organs by the brain. Efferent
fiber activity modulates the gain of electromechanical motors in both the auditory and
vestibular system. The ability of olivocochlear fiber activity to alter the gain of the cochlear
amplifier is well established with strong evidence that it facilitates the detection of acoustic
signals in a noisy environment. New findings suggest the OC system may play a role in
sensory plasticity but the roles of the MOC and LOC in these processes are as yet unclear.
Acoustic activation of olivocochlear fibers is used in the clinic to test the integrity of the
outer hair cell function. The structural and functional similarities of efferent stimulation of
the auditory and vestibular portions of the inner ear offer hope that testing procedures may
be developed that will allow reliable testing of the vestibular hair cell function.
Acknowledgments
We thank Dr. JJ Guinan for providing the outline and structure for this review in his 2010 review of olivocochlear
efferents in Current Opinion in Otolaryngology & Head and Neck Surgery. Supported by NIH NIDCD RO1s
DC004928 (RDR) and DC000384/DC002775 (WEB)
Supported by NIDCD R01s DC004928/DC006685 (RDR) and DC000384/DC002775 (WEB)
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References and recommended reading
Papers of particular interest, published within the annual period of review, have been
highlighted as:
* of special interest
** of outstanding interest
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KEY POINTS
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•
Efferent fiber activity modulates the gain of electromechanical motors in both
the auditory and vestibular system.
•
Olivocochlear (OC) fiber activity alters the gain of the cochlear amplifier and
improves the detection of acoustic signals in a noisy environment.
•
New findings suggest the OC system may play a role in sensory plasticity but
the roles of the medial OC and lateral OC in these processes are as yet unclear.
•
Acoustic activation of olivocochlear fibers provides an objective clinical test for
the functional integrity of outer hair cells.
•
The structural and functional similarities of inner ear sensory epithelia offer
hope that testing procedures based on activation of the efferent vestibular
system (EVS) may be developed that would allow testing of vestibular hair cell
function.
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